Regulatory mechanism of doaminergic signal transduction in the striatum-bichemical studies.

本研究试图从生化和药理学角度阐明纹状体多巴胺受体的作用机制，并探讨多巴胺能神经元活动的调控机制。结果表明：采用Berbridge‘s方法，用大鼠纹状体进行切片实验，观察多巴胺或阿朴吗啡等混合多巴胺受体激动剂对磷脂酰肌醇的转化作用。用SCH 23390或螺环酮进行的抑制实验表明，PI翻转的这种增强依赖于多巴胺D2受体。下一步，通过腹腔注射CCK 8类似物来观察CCK对大鼠脑皮质多巴胺释放的影响。为此，进行了体内微循环实验，结果表明CCK对多巴胺的释放有促进作用。此外，还从即刻早期基因的角度研究了神经肽与多巴胺的关系。结果表明，戊四唑诱导的c-fos激活可被BTH、CCK和神经激肽抑制，这种抑制作用可被多巴胺拮抗。此外，我们还证实了这些神经肽抑制了大鼠层酪氨酸羟基酶基因的表达。应该强调的是，在多巴胺和神经肽的信号转导之间存在着两种串扰，即基因组和非基因组。

In this studies, we tried to elucidate functional mechanism f doamine receptors in the striatum from biochemical and pharmacological viewpoints and discuss on mechanisms by which dopaminergic neuronal activtes are regulated. As results, following results were obtained.By means of slice experiments following Berridge's methds using rat striatum, phospatdyl inositol turnover stimulated by mixed dopamineagnist such as doamine or apomorphine was xamined. As results, increases of PI, P2, P3 reeases were bserved and these increases were dose-dependent.Inhibiton experiments by use of SCH 23390 or spiperone revealed that this acceeratin of PI turnver was dependent upon doamine D2 receptors.As next step, cerulein, a CCK 8 analog was ntraperitoneally injected to observe how CCK had effects on dopamine release from rat stratum. For this urpose, in vivo microdialsis experiments were done with the result of increasing effect of CCK on doamine release. In addition, relationship between neuropeptide and dopamine was studied from a viewpoint of immediate early genes. It was noticed that pentylentetrazole indused activation of c-fos was inhiited by bth CCK and neurokinin and such inhibition was antagonized by doamine. Furthermore, we confirmed that these neuropeptide inhibited gene expresion of tyrosine hydroxylase in rat stratum. Emphasis should be put on the fact that there were two hases of crosstalk, i.e. genomic and non-genomic, between sgnal transduction of dopamine and neuropeptides.